Efficacy and mechanisms of combined aerobic exercise and cognitive training in mild cognitive impairment: study protocol of the ACT trial

Fang Yu, Feng Vankee Lin, Dereck L Salisbury, Krupa N Shah, Lisa Chow, David Vock, Nathaniel W Nelson, Anton P Porsteinsson, Clifford Jack Jr, Fang Yu, Feng Vankee Lin, Dereck L Salisbury, Krupa N Shah, Lisa Chow, David Vock, Nathaniel W Nelson, Anton P Porsteinsson, Clifford Jack Jr

Abstract

Background: Developing non-pharmacological interventions with strong potential to prevent or delay the onset of Alzheimer's disease (AD) in high-risk populations is critical. Aerobic exercise and cognitive training are two promising interventions. Aerobic exercise increases aerobic fitness, which in turn improves brain structure and function, while cognitive training improves selective brain function intensively. Hence, combined aerobic exercise and cognitive training may have a synergistic effect on cognition by complementary strengthening of different neural functions. Few studies have tested the effects of such a combined intervention, and the findings have been discrepant, largely due to varying doses and formats of the interventions.

Methods/design: The purpose of this single-blinded, 2 × 2 factorial phase II randomized controlled trial is to test the efficacy and synergistic effects of a 6-month combined cycling and speed of processing training intervention on cognition and relevant mechanisms (aerobic fitness, cortical thickness, and functional connectivity in the default mode network) in older adults with amnestic mild cognitive impairment. This trial will randomize 128 participants equally to four arms: cycling and speed of processing, cycling only, speed of processing only, or attention control for 6 months, and then follow them for another 12 months. Cognition and aerobic fitness will be assessed at baseline and at 3, 6, 12, and 18 months; cortical thickness and functional connectivity at baseline and at 6, 12, and 18 months; Alzheimer's disease (AD) conversion at 6, 12, and 18 months. The specific aims are to (1) determine the efficacy and synergistic effects of the combined intervention on cognition over 6 months, (2) examine the underlying mechanisms of the combined intervention, and (3) calculate the long-term effect sizes of the combined intervention on cognition and AD conversion. The analysis will use intention-to-treat and linear mixed-effects modeling.

Discussion: This trial will be among the first to test the synergistic effects on cognition and mechanisms (relevant to Alzheimer's-associated neurodegeneration) of a uniquely conceptualized and rigorously designed aerobic exercise and cognitive training intervention in older adults with mild cognitive impairment. It will advance Alzheimer's prevention research by providing precise effect-size estimates of the combined intervention.

Trial registration: ClinicalTrials.gov, NCT03313895 . Registered on 18 October 2017.

Keywords: Aerobic exercise; Aerobic fitness; Alzheimer’s disease; Cognitive training; Executive function; Memory; Neuroimaging.

Conflict of interest statement

Authors’ information

Provided on the title page.

Ethics approval and consent to participate

This study was approved by the University’s IRB. The consent process was detailed in the manuscript.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Schedule of enrollment, interventions, and assessments

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